Technologies relating to production method and application of a silica particle or a silica sphere have been studied and developed throughout the world in great variety of ways, and a part of these technologies are put into practical use in improvement of incandescent lamp, bioassay, or the like. For synthesis thereof, usual practice is used or TEOS (tetraethylorthosilane; hereafter to be abbreviated as “TEOS”) is normally used as the starting material, and conventional silica particles are TEOS particles. However, since surface layer of such TEOS particles has lower chemical reactivity (binding ability to foreign protein or nucleic acid), activation by introduction of acceptor group based on a silica compound other than the TEOS has been attempted (Patent Document 1). For example, as silica compound, tetraethoxysilane (OH group), mercapto-propylethoxysilane (SH group), amino-propylethoxysilane (NH2 group) (one in parenthesis is “acceptor group” to be introduced) and the like are known. In other words, conventional activated silica particles have double structure composed of inner shell comprising TEOS and outer shell comprising acceptor group, and costs of time, labor, and the like required for producing thereof have been expensive. As described above, conventionally, preparation of silica particle has been generally made using tetraethoxysilane (TEOS) and the number of reports dealing with preparation of particles from other silica compounds such as MPS is small. The reason for this is considered that while the number of binding sites (Si—O) for silica network formation is four in TEOS, preparation of the particle by selecting other silica compounds with binding site inevitably three or less is not easy task. In fact, even if preparation of particles is attempted by MPS under particle preparation conditions using ordinary TEOS, particles are not prepared favorably. Further, among cases where MPS or the like is actually used, in the production of the MPS, the technology for obtaining MPS particle is known (Patent Document 2) in which MPS are pretreated (for 2-5 days at room temperature) with only hydrochloric acid (or mixed solution of hydrochloric acid and cetylmethylammonium chloride), ammonia water is added thereto and mixed, and are further reacted for 2 days at room temperature. However, this technology has such drawbacks that it lacks progressivity with regard to production costs as compared with conventional technology, production process is cumbersome and impractical, and the number of days required for producing particle is significant. In addition, adjustments of size (particle diameter) of particles thus prepared are difficult.
MPS particles obtained according to the method disclosed by Patent Document 2 is advantageous in that cavity formation characteristics is high and surface area is expanded due to cavities formed. However, in light of the fact that the technology as described in Patent Document 1 has been already developed, in which functional materials are bound to silica compound to be mixed with reaction solution for particle formation, and incorporated to particle lattice to allow functional materials to be contained in particle at high concentration, the amount of functional materials which may be contained in one particle becomes higher with lower cavity formation characteristics, and this is useful by just that much, and therefore, the method described in Patent Document 2 resulting in higher cavity formation characteristics can not be said to be useful for a case where the object is to take functional materials. As for the cavity formation characteristics, when cavity formation characteristics is high in the particle, internal structure is reduced and site where functional materials can be arranged is reduced, and this is disadvantageous for internal functionalization (fluorescence intensity per one particle is low). Further, when cavity formation characteristics is high, although surface area increases in some case, there are problems of control of void content and control of functional material arrangement (quantitative arrangement is difficult), and therefore, this can not be said to be useful unless effective embodiment is exemplified. Meanwhile, when cavity formation characteristics is low, internal structure increases, site where functional materials can be arranged increases, and this is advantageous for internal functionalization (fluorescence intensity per one particle is high). Further, with lower cavity formation characteristics, the surface area is simple surface area only, this surface area correlates with particle diameter, quantitative arrangement of functional materials becomes possible, and this is useful for quantitative analysis. Therefore, it can be said that one of superiorities which “non-pored” particle has to be utilized as size marker or fluorescent marker is high ability of internal functionalization.
In regard to adsorptive capacity characteristics of silica to DNA, protein or the like, with particles having many pores as described in Patent Document 2, effective adherence area to which DNA and protein adhere is not depending on surface area only based on diameter of particles, and adherence surface area varies according to size, number, position of pores, and it is therefore considered that parameters of adherence area are diversified, thereby causing a problem with quantitative characteristics. (It is considered that a difference is easily caused within a lot prepared and between lots prepared, and no finding is shown in Patent Document 2 that quantification was actually possible.) Therefore, if non-pored silica particles are realized, effective adherence area simply depends on particle diameter of the particle, surface area can then be determined by particle size, which is advantageous for quantitative experiments, and there are needs for preparation of such particles.    Patent Document 1: International publication WO No. 2006/070582 pamphlet    Patent Document 2: International publication WO No. 2003/002633 pamphlet